Grant: CIHR Fellowship

Important secreted-protein signaling loops exist in several cancers that sustain their growth and promotes cancer cell proliferation. Evidence suggests that persistent DNA damage due to genome instability in certain cancers results in cytoplasmic DNA that causes persistent activation of cellular signaling proteins called cGAS and STING. cGAS is an enzyme present in the cytoplasm that binds cytoplasmic DNA and catalyzes the formation of a small molecule called cGAMP. cGAMP can bind to the adaptor protein STING, which results in the activation of immune signaling and cytokine protein production. There are several cancers, such as multiple myeloma, fibrosarcoma, malignant astrocytoma and a mouse melanoma, that require the constant presence of certain cytokine or growth factor proteins to survive and/or proliferate. From our unpublished and preliminary data, we have discovered that in certain biological contexts the cGAS-STING pathway can cause constant production of some of the same cytokines and growth factor proteins that the aforementioned cancers require. We propose that in several cancers, the cGAS-STING pathway is critical for tumor-promoting protein-secretion loops. Verification of our findings could identify previously unknown signaling network relationships and will suggest the viability of new cancer therapy drugs that block the cGAS-STING pathway.